Project Abstract Accurate diagnosis of prostate cancer is essential for individualized treatment decisions. With more recent advances in multiparametric magnetic resonance imaging (mpMRI), suspicious cancer lesions can be identified. Co-registered MRI-ultrasound fusion targeted biopsy (MRF-TB) allows the sampling of specific lesions of concern within the prostate has emerged as the preferred diagnostic procedure for men presenting with a concern for prostate cancer. As the use of targeted prostate biopsy techniques expands, a biopsy needle that can accurately and reproducibly obtain tissue samples from the targeted sites along the anticipated biopsy path is crucial for high diagnostic accuracy. The biopsy needles currently available do not meet this need. Targeted prostate biopsy procedure has two phases: (I) needle positioning and (II) needle firing. The current needle delivery process and needle design cause the undesired intraoperative prostate movement in Phase I and significant needle deflection in Phase II, making the desired biopsy core trajectory difficult to achieve. This leads to variance in the targeted and actual locations of the obtained acquired tissue core. Such sampling errors result in a lesion undersampling, false negative results and misdiagnosis. This research aims to establish the effectiveness of our novel prostate needle biopsy device designed specifically to optimize lesion sampling accuracy in co-registered MRF-TB. To reduce sampling errors in Phase II, we developed a dual-bevel stylet tip. In a preliminary biopsy study using the prostate-like tissue phantom, this stylet tip reduced needle deflection by 77% when compared to the current needle design and demonstrated the sequentially equivalent core length using a commercial biopsy actuation device. To account for the prostate movement in Phase I, we developed a mosquito proboscis-inspired (MPI) needle with incremental needle-stylet motion and micro-notched stylet. The MPI needle can reduce the targeted organ movement by up to 34% (p < 0.001) in a prostate-like tissue phantom when compared to the current needle delivery process. The aforementioned innovations demonstrate greater needle sampling accuracy when compared to the current industry standard needles. This research proposes to combine these innovations in a novel prostate needle biopsy device to demonstrate the optimal sampling accuracy and acquire adequate preclinical validation. This research will have significant impact on patients presenting with a concern for prostate cancer. Our innovations will reduce false negative biopsy results and increase the biopsy diagnostic accuracy with a more expedient and less traumatic biopsy procedure. The proposed technique may further benefit other organ biopsy procedures (e.g. the liver biopsy) as well as other clinical practices requiring precise needle deployment.